The significant loss of promoter activity in Sp1 mutant construct suggests that binding of Sp1 transcription factor to its cognate motif in TATA-less hres gene promoter is an important step in the initiation of transcription and is responsible for maintaining the basal level of resistin gene expression in U937 cells.
The similarity in the results obtained using two different series of mutant constructs strongly suggested that A and B were bona fide regulatory elements.
We found that expression of the mutants was comparable to that of the WT construct, but although the WT construct was able to restore cohesion, neither of the cancer-associated mutant constructs could, suggesting that tumor cells bearing these mutations have compromised centromeric cohesion.
Transfection experiments with mutant L protein constructs suggest that both types of deletion trigger endoplasmic reticulum (ER) stress, resulting in oxidative stress and DNA damage.
This is supported by studies expressing phosphorylation-null and phosphomimetic point mutant constructs in cells, suggesting that S405/S418 phosphorylation plays a critical role in regulating cellular actin polymerization necessary to promote cell migration [41] and invadopodia function [26].
In cultured cell models of mutant htt toxicity, expression of N118-120Q was reported to produce less activation of caspase 3 than expression of N171-82Q consuggestinguggesthat thet the N118 fragment is less toxic (21).
In contrast, no significant differences were observed in either cell line with the mutant Ebox-952 construct, suggesting a negligible role in FPGS expression.
After 24 h, the DHODH mRNA levels were equal for the wild-type and the three mutant constructs (results not shown), suggesting that the G152R and R346W mutant proteins showed reduced protein expression or increased protein turnover.
Furthermore, the modeled interactions together with the mutant construct binding studies suggest that this conserved cleft is a site of favorable lipid interaction for both cholesterol and stearic acid.
Additionally, Kv11.1-mut constructs alone did not produce any measurable tail currents, suggesting that mutant constructs did not form functional channels.
